Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B.

Collart, Martine; Baeuerle, P; Vassalli, Pierre

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Title		Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B.
Authors		Collart, Martine Baeuerle, P Vassalli, Pierre
Published in		Molecular and Cellular Biology. 1990, vol. 10, no. 4, p. 1498-506
Abstract		This study characterizes the interaction of murine macrophage nuclear proteins with the tumor necrosis factor alpha (TNF-alpha) promoter. Gel retardation and methylation interference assays showed that stimulation of TNF-alpha gene transcription in peritoneal exudate macrophages was accompanied by induction of DNA-binding proteins that recognized with different affinities four elements related to the kappa B consensus motif and a Y-box motif. We suggest that the basal level of TNF-alpha expression in macrophages is due to the binding of a constitutive form of NF-kappa B, present at low levels in nuclei from resting thioglycolate exudate peritoneal macrophages, to some if not all of the kappa B motifs; we postulate that this constitutive form contains only the 50-kilodalton (kDa) DNA-binding protein subunits of NF-kappa B, not the 65-kDa protein subunits (P. Baeuerle and D. Baltimore, Genes Dev. 3:1689-1698, 1989). Agents such as glucocorticoids, which decrease TNF-alpha transcription, diminished the basal level of nuclear NF-kappa B. Stimulation of Stimulation of TNF-alpha transcription in macrophages by lipopolysaccharide, gamma interferon, or cycloheximide led to an increased content of nuclear NF-kappa B. This induced factor represents a different form of NF-kappa B, since it generated protein-DNA complexes of slower mobility; we propose that this induced form of NF-kappa B contains both the 50- and 65-kDa protein subunits, the latter ones being necessary to bind NF-kappa B to its cytoplasmic inhibitor in uninduced cells (Baeuerle and Baltimore, Genes Dev., 1989). In resting cells, this inducible form of NF-kappa B was indeed detectable in the cytosol after deoxycholate treatment. UV cross-linking experiments and gel retardation assays indicated that the inducible form of NF-kappa B is in a higher-order complex with other proteins.
Keywords		Animals — Base Sequence — Cell Nucleus/metabolism — Cells, Cultured — Cycloheximide/pharmacology — DNA Probes — Gene Expression Regulation — Lipopolysaccharides/pharmacology — Macrophage Activation — Macrophages/drug effects/physiology — Mice — Mice, Inbred CBA — Molecular Sequence Data — NF-kappa B — Nuclear Proteins/biosynthesis/metabolism — Promoter Regions, Genetic — Templates, Genetic — Transcription Factors/genetics/metabolism — Transcription, Genetic — Tumor Necrosis Factor-alpha/genetics
Identifiers		DOI: 10.1128/mcb.10.4.1498 PMID: 2181276
Full text		Article (Published version) (2.5 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire
Research group		Groupe Collart Martine (microbiologie et médecine moléculaire) (81)
Citation (ISO format)		COLLART, Martine, BAEUERLE, P, VASSALLI, Pierre. Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. In: Molecular and Cellular Biology, 1990, vol. 10, n° 4, p. 1498-506. https://archive-ouverte.unige.ch/unige:30049

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Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B.